levetiracetam and Migraine-Disorders

Migraine is characterized by moderate to severe recurrent headache lasting for 4-72 h. Cortical hyperexcitability may play a crucial role in migraine onset. Therefore, antiepileptic drugs, such as levetiracetam, may be beneficial.. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of levetiracetam in migraine prophylaxis. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on migraine prophylaxis and levetiracetam published before May 2020. The main outcomes were number of patients with >50% headache frequency reduction, frequency of headache, and headache severity.. We identified 4 RCTs involving 192 patients and 4 prospective studies involving 85 patients. The overall data on number of patients with >50% headache frequency reduction, headache frequency, and headache severity were subjected to meta-analysis, which revealed significant differences between the levetiracetam and the placebo groups (risk ratio [RR] of number of patients with >50% headache frequency reduction = 0.46, 95% confidence interval [CI] = 0.35 to 0.61; weighted mean difference [WMD] of headache frequency per month = -3.78, 95% CI = -5.52 to -2.03; standard mean difference [SMD] of headache severity = -2.42, 95% CI = -4.47 to -0.37).. Our study indicated that levetiracetam can significantly reduce headache frequency and severity in adults and children. Thus, oral levetiracetam can be a therapeutic option for migraine prophylaxis, especially concerning with the adverse effects or teratogenicity of other preventive treatments.

Topics: Anticonvulsants; Headache; Humans; Levetiracetam; Migraine Disorders; Prospective Studies

The aim of this systematic review was to evaluate current evidence on the efficacy and safety of levetiracetam as migraine prophylaxis in adult patients suffering from migraine attacks.. PubMed, Scopus, Cochrane Central Register of Controlled Trials, and International Web of Science were searched (last search in August 2018) for studies investigating levetiracetam for migraine prophylaxis in adults. Both randomized and non-randomized trials were eligible. Efficacy was the primary outcome, but tolerability was also investigated. The study is registered on PROSPERO, number CRD42018088900.. Nine studies, enrolling 215 patients, were included. Levetiracetam decreased the frequency of attacks with headache in all studies, with a pooled mean difference of -3.02 (95% CI: -4.59 to -1.45; I. Levetiracetam may be a relatively safe and efficacious treatment for the prophylaxis of migraine based on limited evidence, most from uncontrolled studies. Further evidence from randomized controlled trials is necessary.

Topics: Adult; Anticonvulsants; Humans; Levetiracetam; Migraine Disorders; Randomized Controlled Trials as Topic; Valproic Acid

Migraine is a common and costly neurological disorder that affects approximately 1 of every 7 people annually. Pharmacological therapy for prevention of migraine is warranted when patients experience at least 6 headache days, 4 headache days with at least some impairment or 3 headache days with severe impairment or requiring bed rest in a month. Levetiracetam is an antiepileptic drug that has the potential to be beneficial for migraine prophylaxis. The objective of this review was to assess the safety and efficacy of levetiracetam for migraine prophylaxis.. A systematic search was conducted in MEDLINE (1946-August 2017), EMBASE (1947-August 2017) and CENTRAL using the terms: migraine disorders, migraine, or headache and etiracetam or levetiracetam. Animal studies, case reports, abstracts, letters to the editor and those not written in English were excluded.. Eleven articles were identified for inclusion. Of the studies included, 2 were retrospective chart reviews, 4 were randomized placebo- or active comparator-controlled trials, and the remaining 5 were prospective, open-label studies. All studies found a statistically significant decrease in headache frequency per month compared to baseline or placebo when used for treatment of episodic migraine (2.96-10.9 headache/mo decrease), and 57.9%-100% of patients had at least a 50% decrease in headache frequency from baseline. Significance was not consistently demonstrated in the prophylactic treatment of chronic migraine. The most common adverse effects noted included somnolence, dizziness and behavioural effects but generally did not require discontinuation.. The studies included in this review indicate that levetiracetam is well-tolerated and may be an alternative treatment option for episodic migraine prophylaxis. Additional clinical evidence is necessary to establish the efficacy of levetiracetam for the prophylactic treatment of chronic migraine.

Topics: Animals; Anticonvulsants; Humans; Levetiracetam; Migraine Disorders; Piracetam; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome

A 26-year-old female presented with vision loss accompanied by migraine-like headaches. A contrast-enhanced magnetic resonance imaging of the brain was performed which revealed findings suggestive of stroke-like migraine attacks after radiation therapy (SMART) syndrome. SMART syndrome is a delayed complication of brain radiation characterized by neurologic symptoms including migraine-like headaches, seizures, and hemispheric impairment. The purpose of this article is to make the readers aware of this rare complication of brain irradiation. Appropriate diagnosis of SMART syndrome is essential to avoid invasive tests.

Topics: Adult; Brain Neoplasms; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Migraine Disorders; Nootropic Agents; Piracetam; Radiation Injuries; Syndrome

Migraine, according to the criteria of the International Headache Society, occurs in about 5 to 10% of children and adolescents. Pediatric migraine can cause a significant impact on quality of life. As stated by the American Academy of Neurology and Child Neurology Society's migraine guidelines, situations for prophylaxis consideration include recurring migraines that significantly interfere with daily activities, despite acute therapy; frequent headaches; contraindication, overuse, or failure of acute therapy; adverse reactions to acute therapy; cost of acute and preventive therapies; patient preferences; and presence of uncommon migraine conditions. Preventive therapy may be warranted in as many as 30% of young patients with migraine seen in tertiary headache centers. Headache related disability can be measured by scoring systems such as the Pediatric Migraine Disability Assessment Scale. Numerous medications have been studied to prevent migraines in children, including antihistamines, antidepressants, and antihypertensive agents. However, few high quality clinical trials actually demonstrate efficacy in this population. Recently, many studies dealt with the use of antiepileptic drugs in this indication but there is a paucity of placebo controlled studies. Both topiramate (TPM) and divalproex sodium have been studied in a randomized-controlled study. Only TPM showed efficacy, though, clearly, further controlled trials are needed to confirm these data. Besides unproven efficacy, adverse effects of valproic acid, such as weight gain, somnolence, and alopecia may limit its use. Additional studies are warranted before recommending levetiracetam (LVT), zonisamide (ZNS) and gabapentin (GBP) agents for migraine prophylaxis in children and adolescents.

Topics: Adolescent; Amines; Anticonvulsants; Child; Cyclohexanecarboxylic Acids; Drug Tolerance; Fructose; Gabapentin; gamma-Aminobutyric Acid; Headache; Humans; Levetiracetam; Migraine Disorders; Piracetam; Placebos; Retrospective Studies; Topiramate; Treatment Failure; Valproic Acid

In this paper we review new treatment options for migraine prevention. We start with an overview about migraine and then briefly discuss current indications for migraine prevention and new and emerging preventive medications.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Anticonvulsants; Antidepressive Agents; Antihypertensive Agents; Calcium Channel Blockers; Coenzymes; Drug Therapy; Humans; Levetiracetam; Lisinopril; Migraine Disorders; Petasites; Piperazines; Piracetam; Preventive Medicine; Triazoles; Ubiquinone

Few drugs are available for migraine prophylaxis in children. Levetiracetam is a broad-spectrum anti-seizure drug that has been suggested to be effective in reducing adult migraine episodes. We assessed the safety and efficacy of levetiracetam in the prevention of pediatric migraine.. A randomized double-blind placebo-controlled trial was performed. Eligible participants were aged 4-17 years old with at least four migrainous episodes monthly or had severe disabling or intolerable episodes. Primary endpoints were the mean changes in monthly frequency and intensity of headaches from the baseline phase to the last month of the double-blind phase. Safety endpoint was the adverse effects reported.. Sixty-one participants (31 taking levetiracetam and 30 taking placebo) completed the study. All had a significant reduction in frequency and intensity of episodes that was significantly greater in the levetiracetam arm. Sixty eight percent of individuals in the treatment group reported more than 50% reduction of episodes at the end of the trial compared with 30% in the placebo group (. Levetiracetam may be useful in migraine prevention and may decrease migraine episodes and severity.. The study is prospectively registered with Iranian Registry of Clinical Trials; IRCT.ir, number IRCT2017021632603N1.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Female; Humans; Levetiracetam; Male; Migraine Disorders; Pain Management; Treatment Outcome

Migraine is not curable, but preventive treatments are usually used to decrease the intensity and frequency of headache attacks. Different therapeutic options are widely studied for chronic migraine (CM), but all of them have different inefficacies.. The aim of this study was to compare the efficacy of levetiracetam versus sodium valproate in the treatment of CM.. A randomized controlled clinical trial was conducted on 62 patients with chronic migraine (30 patients in intervention group-treated with levetiracetam and 32 patients in control group- treated with sodium valproate). The treatment regimen consisted of initial dose of levetiracetam or sodium valproate 500 mg daily which increased to 500 mg two times a day after two weeks. The treatment response was evaluated by measuring pain frequency, pain severity, and the MIDAS (migraine disability assessment) score over three months follow-up.. During a three-month follow-up, the mean of headache frequency, severity, and MIDAS score were changed significantly. The rate of decrease in headache frequency was higher in control group than intervention group ((6.7±2.7 and 14.4±5.3 day/month, respectively) (P<0.001). Also, headache severity and MIDAS score significantly decreased in the control group than intervention group (3.4±1.1 and 5.7±1.6, respectively P<0.001, 16.7 ± 6.1 and 30.2±9.8, respectively (P<0.001).. According to our findings, levetiracetam offered improvement in headache frequency, severity, and MIDAS score in patients with CM. However, levetiracetam was not effective enough for chronic migraine as valproate, despite some significant effect. Thus levetiracetam can be one of the choices for limited chronic migraine subjects who are in contraindication of Valproate.

Topics: Adolescent; Adult; Analgesics; Chronic Disease; Disability Evaluation; Double-Blind Method; Female; Humans; Iran; Levetiracetam; Male; Middle Aged; Migraine Disorders; Pain Measurement; Piracetam; Severity of Illness Index; Time Factors; Treatment Outcome; Valproic Acid; Young Adult

In the last years, the hypothesis that cortical hyperexcitability may play a role in the physiopathology of migraine led to the therapeutic use of some antiepileptic drugs. To evaluate the efficacy of levetiracetam as prophylactic treatment for migraine without aura in elderly patients. We performed a small open-label trial treating 13 elderly patients(8F 5M) mean age 64.7 years (SD 3.4), range 60-72 years affected by migraine without aura (ICDH '04 criteria). The mean age of disease was 21.3 years (SD13.4) range 2-45 years. At baseline: the frequency of attacks was 12.2/month (SD 5.9), range 6-25; the mean number of drugs for acute attacks was 12.6 (SD 6.5) tablets/month. All patients took concomitant medication for other chronic diseases. After recruitment Levetiracetam 500 mg/die was administered for 1 week and 1000 mg/die for six months. The basal frequency of attack was 12,2 (SD 5.9) and 8,3 (SD 4.9), 4,1 (SD2.6), 1,3 (SD1.4) after 1, 3 and 6 months respectively [P=0.079; P<0.0001; P<0.0001].The basal value of intaking drugs for acute attacks was 12,6 (SD 6.5) and 6,7 (SD 4.3), 2,8 (SD 2.2), 1,4 (SD1.7) after 1, 3 and six months respectively [P=0.012; P<0.0001; P<0.0001](T-test analysis). Levetiracetam was well tolerated (7 patients complained somnolence, lack of concentration and gastralgia but none patient withdrew the study). In our study levetiracetam showed a good efficacy in frequency and intensity reduction of headache attack and showed a very good tolerability despite all elderly patients took drugs for concomitant diseases.

Topics: Aged; Anticonvulsants; Female; Humans; Levetiracetam; Male; Middle Aged; Migraine Disorders; Piracetam; Treatment Outcome

Recent theories about migraine pathogenesis have outlined an abnormal central processing of sensory signals, also suggested by an abnormal pattern of EEG hyper-synchronization under visual stimulation. The aim of the present study was to test the efficacy of topiramate and levetiracetam vs placebo in a double blind project observing the effects of the three treatments on the EEG synchronization in the alpha band under sustained flash stimulation.. Forty-five migraine without aura outpatients (MO) were selected and randomly assigned to 100mg topiramate, 1000 mg levetiracetam or placebo treatment. In addition, 24 non-migraine healthy controls were submitted to EEG analysis. The EEG was recorded by 19 channels: flash stimuli with a luminosity of 0.2J were delivered, in a frequency range from 3 to 30 Hz. We evaluated the phase synchronization index, that we previously applied in migraine, after EEG signals filtering in the alpha band. Our approach was based on the Hilbert transform.. Both levetiracetam and topiramate significantly decreased migraine frequency, compared with placebo. MO patients displayed increased alpha-band phase synchronization as an effect of stimulus frequency; on the other hand the stimuli had an overall desynchronizing effect on control subjects. The phase synchronization index separates the two stages, before and after the treatment, only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz.. An abnormal alpha band synchronization under visual stimuli was confirmed in migraine; this phenomenon was reversed by levetiracetam preventive treatment.. These results confirmed in humans the inhibiting action of levetiracetam on neuronal hyper-synchronization.

Topics: Adolescent; Adult; Algorithms; Alpha Rhythm; Brain Mapping; Cortical Synchronization; Double-Blind Method; Electroencephalography; Evoked Potentials, Visual; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Nootropic Agents; Photic Stimulation; Piracetam; Topiramate

The prophylactic treatment of migraine includes anticonvulsant drugs such as valproic acid and topiramate. However, these substances are often poorly tolerated by migraine patients. So far levetiracetam has hardly been studied as an episodic migraine prophylactic agent in adults.. To perform a prospective pilot study for the evaluation of the efficacy and tolerability of levetiracetam in the prophylactic treatment of episodic migraine.. Fifty patients with episodic migraine were enrolled in this prospective, open label study. After a baseline period of four weeks, patients received 1,000 mg (starting dose 500 mg) bid levetiracetam for 12 weeks. Migraine frequency and accompanying symptoms were recorded in a headache diary. The primary endpoint was the comparison of attack frequency during the baseline with attack frequency during the last four weeks of treatment (treatment period 3).. In the Intent-To-Treat analysis, 46% of the patients had a migraine reduction of more than 50% in the third period as compared to the baseline period. The mean number of migraine attacks decreased from 5.2 +/- 2.1 (baseline) to 3.4 +/- 2.7 (period 3). The most frequently reported side effects were somnolence, nausea, and weight gain; all were mild and transient. In a post-hoc comparison, responders to levetiracetam had significantly less migraine attacks at baseline and had significantly more often migraine with aura.. The data suggest that levetiracetam has some potential in the prophylactic treatment of episodic migraine which seems, however, to be not superior to that of other anticonvulsant drugs. Levetiracetam was well tolerated and showed better efficacy in patients with migraine with aura and in less affected migraine patients. A larger placebo-controlled, double-blind study in adults seems justified on the basis of these data.

Topics: Adult; Anticonvulsants; Double-Blind Method; Humans; Levetiracetam; Migraine Disorders; Migraine with Aura; Pilot Projects; Prospective Studies; Topiramate; Treatment Outcome; Valproic Acid

Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear.. To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy.. A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018.. Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared.. Antiepileptic drug treatment pattern according to seizure type and comorbidities.. Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).. Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Topics: Adolescent; Adult; Anticonvulsants; Anxiety Disorders; Comorbidity; Dissociative Disorders; Epilepsies, Partial; Epilepsy, Generalized; Female; Headache Disorders; Humans; Lamotrigine; Levetiracetam; Mental Disorders; Migraine Disorders; Mood Disorders; Oxcarbazepine; Phenytoin; Retrospective Studies; Risk; Teratogens; Topiramate; Valproic Acid; Young Adult

Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.

Topics: Animals; Benzyl Alcohols; Disease Models, Animal; Dura Mater; Glucosides; Levetiracetam; Male; Medicine, Chinese Traditional; Migraine Disorders; Neurons, Afferent; Nociceptive Pain; Pain Management; Propranolol; Pyrazines; Rats, Sprague-Dawley; Trigeminal Nerve

To explore alterations in γ-aminobutyric acid (GABA) levels in response to levetiracetam (LEV) treatment in patients with migraine. Patients with migraine (N=14) were treated with LEV for 12 weeks. The levels of GABA+ in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and the posterior cingulate cortex (PCC) were examined by proton magnetic resonance spectroscopy before (baseline) and after treatment. LEV showed good efficacy in the reduction of headache frequency and intensity in patients with migraine. Among the 14 patients, good-quality spectral data of GABA+ in the PCC region were obtained in 11 patients. There was a significant decrease in GABA+ levels in the PCC region after LEV treatment. ACC/mPFC GABA+ was assessed by proton magnetic resonance spectroscopy in eight patients with migraine. LEV had no significant effect on GABA+ levels in the ACC/mPFC region. The decreased GABA+ levels after LEV treatment in patients with migraine suggest that GABA is a migraine biomarker.

Topics: Adolescent; Adult; Anticonvulsants; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Levetiracetam; Magnetic Resonance Spectroscopy; Male; Middle Aged; Migraine Disorders; Treatment Outcome; Young Adult

Migraine is common in the pediatric population. Levetiracetam, an anti-epileptic drug, has shown some efficacy in small prospective adult headache studies.. We prospectively evaluated levetiracetam in an open-label study in 20 pediatric migraine patients to assess tolerability and efficacy.. Eighteen of 20 patients had significant reduction in headache frequency. PedMIDAS showed significant decrease in disability scores, side effects were minimal (mild behavioral changes).. Levetiracetam had some efficacy in reducing migraine frequency and disability. Further larger studies are warranted, possibly utilizing a placebo-controlled design.

Topics: Adolescent; Anticonvulsants; Child; Female; Humans; Levetiracetam; Male; Migraine Disorders; Piracetam; Prospective Studies; Treatment Outcome

Topics: Adult; Anticonvulsants; Female; Humans; Infusions, Intravenous; Levetiracetam; Migraine Disorders; Piracetam

Headache is a frequent occurrence among children and adolescents. Chronic headaches can be severe and disabling, and require prophylactic treatment; however, additional data on the use of prophylactic medications for migraine in children are needed.. To review the efficacy and safety of levetiracetam (Keppra) in pediatric patients with a history of recurrent headache.. Data from 19 pediatric patients were retrospectively reviewed. The initial dose of levetiracetam was usually 125 or 250 mg twice daily, but varied depending upon clinical judgment.. Charts of 9 girls and 10 boys (mean age, 11.9 years) were reviewed. A variety of medications, including triptans, had been used before initiating treatment with levetiracetam. Mean headache frequency before treatment was 6.3 per month (standard deviation [SD], 3.8; confidence interval [CI], 4.4 to 8.1). Duration of headaches ranged from 0.25 to 8 years. Migraine (63.2%) and migraine with aura (15.8%) were the most common types of headache reported. Most patients (89.5%) had headaches that were severe. After treatment, the mean headache frequency decreased to 1.7 per month (SD, 2.7; CI, 0.4 to 3.0), representing a reduction compared with baseline (P <.0001). Levetiracetam eliminated headaches in 10 patients (52.6%), and 7 patients (36.8%) had less severe and less frequent headaches. Levetiracetam did not have an effect on headaches in 2 patients (10.5%). Mean duration of treatment with levetiracetam was 4.1 months. Doses ranged from 125 to 750 mg twice daily. Sixteen patients (84.2%) reported no side effects on levetiracetam. One patient experienced asthenia/somnolence and dizziness, and irritable, hyperactive, and hostile behavior led to discontinuation of levetiracetam in another patient. A third patient experienced irritability and moodiness that attenuated after 1 month of treatment and did not require discontinuation.. In this small retrospective review, levetiracetam was found to be generally well tolerated and appears to be a promising candidate for additional evaluation in well-controlled clinical trials of pediatric patients with migraine.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Levetiracetam; Male; Migraine Disorders; Piracetam; Recurrence; Retrospective Studies; Treatment Outcome